Upconversion is a process where low-energy light, usually near-infrared (NIR) or infrared (IR), is converted to higher energies, ultraviolet (UV) or visible, via multiple absorptions or energy transfers (Scheps et al. Prog. Quant. Electr. 1996, 20, 271-358 and Auzel et al. Chem. Rev. 2004, 104, 139-173). This phenomenon has been observed in transition metal, lanthanide, and actinide ions doped into a solid-state host, though the highest efficiencies are found in lanthanide-doped materials.
Recent publications have reported upconversion from colloids of either cubic (α) or hexagonal (β) NaYF4 nanocrytals (Heer et al. Adv. Mater. 2004, 16, 2102-2105; Zeng et al. Adv. Mater. 2005, 17, 2119-2123; Aebischer et al. Chem. Phys. Lett. 2005, 407, 124-128; and Suyver et al. Opt. Mater. 2005, 27, 1111-1130). To date, the highest upconversion efficiencies observed have been in hexagonal-phase NaYF4 bulk materials doped with the Er3+/Yb3+ or Tm3+/Yb3+ ion couples synthesized via solid-state methods (Kramer et al. Chem. Mater. 2004, 16, 1244-1251 and Suyver et al. Lumin. 2005, 114, 53-59).
Colloids of upconverting NaYF4 nanocrystals have been synthesized through thermal decomposition, precipitation, and high-pressure reactions. (Heer et al. Adv. Mater. 2004, 16, 2102-2105; Suyver et al. Opt. Mater. 2005, 27, 1111-1130; Zeng et al. Adv. Mater. 2005, 17, 2119-2123; Mai et al. J. Am. Chem. Soc. 2006, 128, 6426-6436; and Aebischer et al. Chem. Phys. Lett. 2005, 407, 124-128).
Other methods for producing NaYF4 nanocrystals as well as other nanocrystals includes that described by Zhang et al. J. Am. Chem. Soc. 2005, 127, 3260; Mai et al. J. Am. Chem. Soc. 2006, 128(19), 6426; Wang et al. Nature 2005, 437, 121; Wang et al. Chem. Commun. 2006, 2557; Yi et al. Nano Letters 2004, 4, 2191; and Yi et al. WO 03/087259 published on Oct. 23, 2003. Method of producing bigger particles, which are therefore not nanocrystals are also known: Sanjurjo et al. WO 99/29801 published on Jun. 17, 1999.
The synthesis and spectroscopy of upconverting nanocrystals has garnered a tremendous amount of attention recently due, among other, to their potential use as biolabels and in biological assays (Heer et al. Adv. Mater. 2004, 16, 2102-2105; Lu et al. J. Mater. Chem. 2004, 14, 1336-1341; Yi et al. Nano Lett. 2004, 4, 2191-2196; Sivakumar et al. J. Am. Chem. Soc. 2005, 127, 12464-12465; Suyver et al. Opt. Mater. 2005, 27, 1111-1130; Wang et al. Angew. Chem., Int. Ed. 2005, 44, 6054-6057; Zeng et al. Adv. Mater. 2005, 17, 2119-2123; Mai et al. J. Am. Chem. Soc. 2006, 128, 6426-6436; Wang and Li, Chem. Comm. 2006, 24, 2557-2559; and Aebischer et al. Chem. Phys. Lett. 2005, 407, 124-128). Upconverting phosphors have a number of properties that make them attractive for use in these tasks (Kuningas et al. Anal. Chem. 2005, 77, 7348-7355; Corstjens et al. IEEE Proc. Nanobiotechnol. 2005, 152, 64-72; Hirai et al. J. Colloid Interface Sci. 2004, 273, 470-477; Rijke et al. Nat. Biotechnol. 2001, 19, 273-276; Hampl et al. Anal. Biochem. 2001, 288, 176-187; and Zijlmans et al. Anal. Biochem. 1999, 267, 30-36).
Upconverting NaYF4 nanocrystals doped with Er3+/Yb3+ have already been successfully applied to analyte and DNA detection (Wang et al. Angew. Chem., Int. Ed. 2005, 44, 6054-6057 and Wang and Li, Chem. Comm. 2006, 24, 2557-2559). The use of upconverting nanophosphors for bioimaging has also been demonstrated (Lim et al. Nano Lett. 2006, 6, 169-174). The majority of current commercialized labels, such as organic dyes and quantum dots (QDs), utilize the Stokes luminescence of the fluorophore under UV, blue, or green excitation in order to detect the analyte. This leads to high background signals and difficulty in choosing an appropriate label because many biological species fluoresce under ultraviolet or visible radiation. The use of upconverting nanocrystals, two-photon dyes, or two-photon QDs removes many of these difficulties (Konig, J. Microsc. 2000, 200, 83-104; Larson et al. Science 2003, 300, 1434-1437; Kuningas et al. Anal. Chem. 2005, 77, 7348-7355; Hirai et al. J. Colloid Interface Sci. 2004, 273, 470-477; Hampl et al. Anal. Biochem. 2001, 288, 176-187; Corstjens, et al. IEEE Proc.-Nanobiotechnol. 2005, 152, 64-72; Niedbala et al. Anal. Biochem. 2001, 293, 22-30; Rijke et al. Nat. Biotechnol. 2001, 19, 273-276; and Denk et al. Science 1990, 248, 73-76). However, the drawback of using dyes or quantum dots is that they require expensive pulse lasers to meet the high power densities necessary to obtain the two-photon effect (Konig, J. Microsc. 2000, 200, 83-104; Larson et al. Science 2003, 300, 1434-1437; Rijke et al. Nat. Biotechnol. 2001, 19, 273-276; and Denk et al. Science 1990, 248, 73-76). In contrast, due to the relative high efficiency of the upconversion process in lanthanide-doped materials, inexpensive 980 nm NIR diode lasers may be employed as the excitation source. The realization of efficient NIR to visible upconverting nanocrystals will therefore unlock a realm of new possibilities in the field of biolabeling and bioassays.
However, at this point, there remains a need for nanocrystals, more particularly NaYF4 nanocrystals, that have improved physical characteristics over that described in the prior art. In fact, it has been shown that the optical properties of nanocrystals are related to their particle size. Thus, smaller nanocrystals are needed. Also, the particle size distribution as well as the shape and the surface of the nanocrystals are related to the ease of producing a colloidal solution of these nanocrystals, to the transparence and stability of this solution and to the quality, reproducibility and uniformity of the spectral response of the nanocrystals. Thus, nanocrystals with uniform particle size and shape are also needed.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.